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Gandhi P.K.,South College | Revicki D.A.,Outcomes Research | Huang I.-C.,St Jude Childrens Research Hospital
BMC Public Health

Background: Evidence is sparse about whether body weight categories in adolescents are associated with differences in pediatric HRQoL rated by adolescents and parents. Additionally, it is unknown whether HRQoL rated by individuals with different body mass index (BMI) weight categories is psychometrically comparable. This study aimed to assess whether difference in pediatric HRQoL rated by adolescents and their parents was explained by BMI weight status, and to test measurement properties of HRQoL items related to weight categories using differential item functioning (DIF) methodology. DIF refers to the situation when the individuals across subgroups rate an item differently (e.g., item score three by one subgroup and four by another) given the same underlying construct. Methods: A cross-sectional study utilizing a sample of parents (n = 323) and their adolescents aged 15-18 years old (n = 323) who enrolled in Florida's Medicaid. Adolescent self-reports and parent proxy-reports of the Pediatric Quality of Life Inventory was adopted to measure pediatric HRQoL. We classified body weight categories as normal weight, overweight, and obesity. A Multiple Indicator Multiple Cause (MIMIC) method was used to assess DIF associated with BMI weight status, especially testing the disparity in the parameters of different weight categories (reference: lower weight category) associated with a response to a HRQoL item conditioning on the same underlying HRQoL. DIF analyses were conducted by adolescent self-reports and parent proxy-reports. Results: Parents reported lower pediatric HRQoL across all domains than adolescents did. Excess body weight (combined overweight and obese) was significantly associated with a greater discrepancy in the rating of emotional and total functioning between adolescents and parents (p < 0.05). DIF associated with BMI weight categories was identified by two items in adolescent self-reports and five items in parent proxy-reports. Conclusions: Adolescents' BMI weight categories significantly contribute to a difference in the rating of pediatric HRQoL by adolescents and parents. © 2015 Gandhi et al. Source

Tieu E.W.,University of Western Australia | Li W.,University of Tennessee Health Science Center | Chen J.,University of Tennessee Health Science Center | Chen J.,South College | And 5 more authors.
Journal of Steroid Biochemistry and Molecular Biology

CYP11A1 hydroxylates vitamin D3 producing 20S-hydroxyvitamin D3 [20(OH)D3] and 20S,23-dihydroxyvitamin D3 [20,23(OH)2D3] as the major and most characterized metabolites. Both display immuno-regulatory and anti-cancer properties while being non-calcemic. A previous study indicated 20(OH)D3 can be metabolized by rat CYP24A1 to products including 20S,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20S,25-dihydroxyvitamin D3, with both producing greater inhibition of melanoma colony formation than 20(OH)D3. The aim of this study was to characterize the ability of rat and human CYP24A1 to metabolize 20(OH)D3 and 20,23(OH)2D3. Both isoforms metabolized 20(OH)D3 to the same dihydroxyvitamin D species with no secondary metabolites being observed. Hydroxylation at C24 produced both enantiomers of 20,24(OH)2D3. For rat CYP24A1 the preferred initial site of hydroxylation was at C24 whereas the human enzyme preferred C25. 20,23(OH)2D3 was initially metabolized to 20S,23,24-trihydroxyvitamin D3 and 20S,23,25-trihydroxyvitamin D3 by rat and human CYP24A1 as determined by NMR, with both isoforms showing a preference for initial hydroxylation at C25. CYP24A1 was able to further oxidize these metabolites in a series of reactions which included the cleavage of C23-C24 bond, as indicated by high resolution mass spectrometry of the products, analogous to the catabolism of 1,25(OH)2D3 via the C24-oxidation pathway. Similar catalytic efficiencies were observed for the metabolism of 20(OH)D3 and 20,23(OH)2D3 by human CYP24A1 and were lower than for the metabolism of 1,25(OH)2D3. We conclude that rat and human CYP24A1 metabolizes 20(OH)D3 producing only dihydroxyvitamin D3 species as products which retain biological activity, whereas 20,23(OH)2D3 undergoes multiple oxidations which include cleavage of the side chain. © 2015 Elsevier Ltd. All rights reserved. Source

Berbari N.F.,University of Alabama at Birmingham | Kin N.W.,University of Alabama at Birmingham | Sharma N.,University of Alabama at Birmingham | Michaud E.J.,South College | And 2 more authors.
Developmental Biology

Tumor necrosis factor alpha receptor 3 interacting protein 1 (Traf3ip1), also known as MIPT3, was initially characterized through its interactions with tubulin, actin, TNFR-associated factor-3 (Traf3), IL-13R1, and DISC1. It functions as an inhibitor of IL-13-mediated phosphorylation of Stat6 and in sequestration of Traf3 and DISC1 to the cytoskeleton. Studies of the Traf3ip1 homologs in . C. elegans (DYF-11), Zebrafish (elipsa), and . Chlamydomonas (IFT54) revealed that the protein localizes to the cilium and is required for ciliogenesis. Similar localization data has now been reported for mammalian Traf3ip1. This raises the possibility that Traf3ip1 has an evolutionarily conserved role in mammalian ciliogenesis in addition to its previously indicated functions. To evaluate this possibility, a Traf3ip1 mutant mouse line was generated. Traf3ip1 mutant cells are unable to form cilia. Homozygous Traf3ip1 mutant mice are not viable and have both neural developmental defects and polydactyly, phenotypes typical of mouse mutants with ciliary assembly defects. Furthermore, in Traf3ip1 mutants the hedgehog pathway is disrupted, as evidenced by abnormal dorsal-ventral neural tube patterning and diminished expression of a hedgehog reporter. Analysis of the canonical Wnt pathway indicates that it was largely unaffected; however, specific domains in the pharyngeal arches have elevated levels of reporter activity. Interestingly, Traf3ip1 mutant embryos and cells failed to show alterations in IL-13 signaling, one of the pathways associated with its initial discovery. Novel phenotypes observed in Traf3ip1 mutant cells include elevated cytosolic levels of acetylated microtubules and a marked increase in cell size in culture. The enlarged Traf3ip1 mutant cell size was associated with elevated basal mTor pathway activity. Taken together, these data demonstrate that Traf3ip1 function is highly conserved in ciliogenesis and is important for proper regulation of a number of essential developmental and cellular pathways. The Traf3ip1 mutant mouse and cell lines will provide valuable resources to assess cilia function in mammalian development and also serve as a tool to explore the potential connections between cilia and cytoskeletal dynamics, mTor regulation, and cell volume control. © 2011 Elsevier Inc. Source

Tuckey R.C.,University of Western Australia | Slominski A.T.,University of Tennessee Health Science Center | Cheng C.Y.S.,University of Western Australia | Chen J.,University of Tennessee Health Science Center | And 4 more authors.
International Journal of Biochemistry and Cell Biology

Lumisterol3 (L3) is produced by photochemical transformation of 7-dehydrocholesterol (7-DHC) during exposure to high doses of ultraviolet B radiation. It has been assumed that L3 is biologically inactive and is not metabolized in the body. However, some synthetic derivatives of L3 display biological activity. The aim of this study was to test the ability of CYP11A1 to metabolize L3. Incubation of L3 with bovine or human CYP11A1 resulted in the formation of three major and a number of minor products. The catalytic efficiency of bovine CYP11A1 for metabolism of L3 dissolved in 2-hydroxypropyl-β-cyclodextrin was approximately 20% of that reported for vitamin D3 and cholesterol. The structures of the three major products were identified as 24-hydroxy-L3, 22-hydroxy-L3 and 20,22-dihydroxy-L3 by NMR. 22-Hydroxy-L3 was further metabolized by bovine CYP11A1 to 20,22-dihydroxy-L3. Both 22-hydroxy-L3 and 20,22-dihydroxy-L3 gave rise to a minor metabolite identified from authentic standard and mass spectrometry as pregnalumisterol (pL) (product of C20-C22 side chain cleavage of L3) and two trihydroxy-L3 products. The capability of tissues expressing CYP11A1 to metabolize L3 was demonstrated using pig adrenal fragments where 20,22-dihydroxy-L3, 22-hydroxy-L3, 24-hydroxy-L3 and pL were detected by LC/MS. Thus, we have established that L3 is metabolized by CYP11A1 to 22- and 24-hydroxy-L3 and 20,22-dihydroxy-L3 as major products, as well as to pL and other minor products. The previously reported biological activity of pL and the presence of CYP11A1 in skin suggest that this pathway may serve to produce biologically active products from L3, emphasizing a novel role of CYP11A1 in sterol metabolism. © 2014 Elsevier Ltd. Source

Michaud E.,South College | Jacques P.F.,Medical University of South Carolina | Gianola F.J.,University of Washington | Harbert K.,South College
Journal of Physician Assistant Education

Purpose To assess the admission policies, experiences, and attitudes of physician assistant (PA) program directors regarding recruiting, admitting, and training military veterans after the announcement of the “Helping Veterans Become Physician Assistants” initiative. Methods A descriptive survey of 22 questions was distributed to all 173 PA program directors in the United States in April 2013. The survey covered years 2011 to 2013, although it was completed in June of 2013. The results of the survey were compared with the results of a similar survey that covered years 2008 through 2010. Results One hundred and five (60.7%) program directors participated in this survey. Veterans were admitted into 88.1% of responding programs and accounted for an average of 4.0% of all students. One-third of programs (33%) accepted transfer credits for veterans’ military training, and 20% accepted credits for off-duty education. One-third (33%) of programs participated in the Yellow Ribbon Program. Almost 60% of programs had military veteran faculty members. Active recruitment of military veteran students occurred in 31.2% of programs. Program directors described multiple benefits of, and barriers to, admitting and educating veterans. Conclusions For the years 2011 through 2013, as compared to 2008 through 2010, there was an increase in the percentage of PA programs that actively recruited veterans, considered veteran status in the admission process, admitted veterans, and contributed to their financial support. There was also an increased percentage of students with military experience matriculating into PA programs. However, barriers still exist for veterans seeking admission into PA programs, the most significant of which is academic preparedness for a graduate-level PA program. © 2015 Physician Assistant Education Association. Source

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